Date of Completion

Spring 5-1-2020

Thesis Advisor(s)

Dr. John Salamone

Honors Major

Biological Sciences

Disciplines

Biology | Neuroscience and Neurobiology | Psychology

Abstract

Major Depressive Disorder (MDD) is characterized by symptoms such as cognitive dysfunctions, inflammatory changes, and motivational symptoms such as amotivation, fatigue, and anergia. While depressed people are commonly treated by traditional antidepressants such as serotonin reuptake inhibitors (SSRIs), previous studies have reported that SSRI medications do not treat fatigue and anergia symptoms well, and in some cases, can even worsen those symptoms. Subjects treated with dopamine (DA) uptake inhibitors, on the other hand, have been less likely to report symptoms of anergia and fatigue compared to those treated with SSRIs. Common DA uptake inhibitors such as methylphenidate and amphetamines, however, have undesirable side effects, so development of atypical DA uptake inhibitors to combat these side effects is needed. Several highly selective atypical DA uptake inhibitors have recently been developed, which are currently being assessed for their effects on effort-based decision making in rodents to model motivational symptoms seen in humans with MDD. This project is assessing a novel atypical DAT inhibitor, CE-158, for its effects on extracellular DA levels in the nucleus accumbens. Microdialysis and high-performance liquid chromatography with electrochemical detection is being used to measure extracellular DA changes at various time points after administration. Elevated nucleus accumbens dopamine has been linked to increases in effort-based decision making and other aspects of motivation, so findings from this study may reveal whether CE-158 could ultimately be used as a suitable treatment option for effort-related motivational dysfunction in humans suffering from MDD. Through this study it was determined that injections of CE-158 significantly increased extracellular DA levels in the nucleus accumbens.

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